1.Efficacy Mechanism of Xianlian Jiedu Prescription Against Colorectal Cancer Recurrence vias Regulating Angiogenesis
Yanru XU ; Lihuiping TAO ; Jingyang QIAN ; Weixing SHEN ; Jiani TAN ; Chengtao YU ; Minmin FAN ; Changliang XU ; Yueyang LAI ; Liu LI ; Dongdong SUN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):79-87
ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer (CRC) and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit, followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group, low-dose Xianlian Jiedu prescription (XLJDP-L) group (6.45 g·kg-1·d-1), medium-dose Xianlian Jiedu prescription (XLJDP-M) group (12.9 g·kg-1·d-1), high-dose Xianlian Jiedu prescription (XLJDP-H) group (25.8 g·kg-1·d-1), and 5-fluorouracil (5-FU) group (1×10-3 g·kg-1·d-1). The mice were euthanized after 14 days of continuous intervention, and recurrent tumor tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry (IHC) was employed to assess the expression of proliferating cell nuclear antigen (Ki67), vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule (CD31) in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 (ANG-2), VEGF, phosphorylated-protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), and phosphatidylinositol 3-kinase (PI3K) in recurrent tumor tissue. ResultsBefore treatment, there were no statistical differences in tumor volume, tumor weight, and body mass among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group, indicating model stability. After treatment, compared with those in the model group, the tumor volume and tumor weight in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01), showing dose dependency. Meanwhile, there were no significant differences in body weight among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group, tumor tissue in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group had loosely arranged cells, increased intercellular spaces, small and shriveled nuclei, light staining, fewer mitotic figures and atypical nuclei, and increased necrotic areas. IHC showed that compared with those of the model group, the positive rates of Ki67, VEGF, and CD31 in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01) in a dose-dependent manner. Western blot results showed that compared with those of the model group, the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly downregulated (P<0.05, P<0.01), and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner (P<0.05, P<0.01). ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2, VEGF, and CD31.
2.Biological Foundation of Colorectal Adenoma Carcinogenesis in Damp-heat Accumulation Syndrome Based on Transcriptome Sequencing and Mechanism of Shenbai Jiedu Prescription
Yuquan TAO ; Haibo CHENG ; Minmin FAN ; Chengtao YU ; Liu LI ; Ye ZHANG ; Mingxin NI ; Meng SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):48-54
ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome, 11 patients with non-damp-heat accumulation syndrome, and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained, and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome, damp-heat accumulation syndrome, and colorectal cancer, and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction (Real-time PCR) was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome, a total of 384 differentially expressed genes were screened, of which 203 were up-regulated genes, and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome, a total of 2 965 differentially expressed genes were screened, of which 2 460 were up-regulated genes, and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken, and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose: β-N-acetylglucosamine beta-1,3-galactosyltransferase activity, N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity, and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series, glycosphingolipid biosynthesis-lacto and neolacto series, and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment, such as FOSB and B3GALT5, in a dose-dependent manner (P<0.05). ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome, and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.
3.Effect of Shenbai Jiedu Prescription on Fecal Metabolomics and Intestinal Flora Distribution in Patients with Colorectal Adenoma
Ye ZHANG ; Mingxin NI ; Meng SHEN ; Yuquan TAO ; Liu LI ; Minmin FAN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):55-63
ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription, their clinical symptoms were observed, and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine (TCM) syndromes of patients after drug administration decreased significantly (P<0.01). The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration, and a total of 106 differential metabolites were screened out (P<0.05). The Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed that arginine-proline metabolism, ferroptosis, glycine, and serine and threonine metabolism were significantly enriched metabolic pathways (P<0.05). Notably, L-4-hydroxyglutamate semialdehyde, glutathione, isopentenyl pyrophosphate, creatinine, 4-acetamido-2-aminobutanoic acid, and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore, the association between these metabolites and different intestinal flora was analyzed, and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium, Eggerthella, and Dialister (P<0.05). ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria, reducing the abundance of harmful bacteria, and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.
4.Research Progress of Traditional Chinese Medicine Compounds in Prevention and Treatment of Colorectal Adenoma: A Review
Meng SHEN ; Ye ZHANG ; Kai CHEN ; Yuquan TAO ; Minmin FAN ; Mingxin NI ; Liu LI ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):64-72
Colorectal adenoma is a benign tumor originating from the mucosal glandular epithelium of the colorectum and belongs to the category of intraepithelial neoplasia. Its etiology and pathogenesis are not completely clear, and some patients have genetic factors. In recent years, with the improvement in living standards, the incidence of colorectal adenoma has gradually increased due to high-fat diets, intestinal flora disorder, and emotional disturbance. As one of the precancerous lesions of colorectal cancer, colorectal adenoma is increasingly threatening human health. Surgical resection is the most direct and effective method for the treatment of colorectal adenoma, but some patients with colorectal adenoma have the possibility of recurrence after resection. At present, there is still a lack of effective prevention and treatment measures for the recurrence of colorectal adenoma. Traditional Chinese medicine (TCM) plays a unique advantage in improving the clinical symptoms of patients with colorectal adenoma and preventing postoperative recurrence and carcinogenesis. Therefore, this review summarized the clinical research and mechanism of TCM compounds in the prevention and treatment of colorectal adenoma in recent years. The clinical study on the prevention and treatment of colorectal adenoma by TCM compounds can be divided into internal treatment, external treatment, and internal and external combined treatment. The internal treatment mainly focuses on strengthening the spleen, and the external treatment includes retention enema, acupoint application, and other methods. The internal and external combined treatment is mainly based on the internal administration of TCM compounds combined with acupuncture, retention enema, and acupoint stimulation. The study on the mechanism of TCM compounds in preventing and treating colorectal adenoma was mainly explored from the aspects of regulating intestinal flora, regulating cell proliferation immune function, and achieving anti-inflammation. This review summarized the research progress of TCM compounds in the prevention and treatment of colorectal adenoma in recent years and provided a reference for future treatment with TCM.
5.Analysis of the characteristics of platelet changes and influencing factors after transcatheter aortic valve implantation
Xiangyu LI ; Haibo ZHANG ; Fangyu YANG ; Shuai ZHENG ; Fei MENG ; Shengxun WANG ; Yuqing JIAO ; Yuehuan LI ; Kaisheng WU ; Jinglun SHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):832-837
Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.
6.Exploration of Integrated Traditional Chinese and Western Medicine Treatment Mode for Malignant Tumors
Junyi WANG ; Liu LI ; Weixing SHEN ; Mianhua WU ; Zhongying ZHOU ; Haibo CHENG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(3):217-222
Malignant tumors are major diseases that seriously threaten human health.Although the integration of traditional Chinese and Western medicine has become an expert consensus on treatment of malignant tumors in China,a mature treatment mode of integrat-ed traditional Chinese and Western medicine has not yet been formed.This paper explores the construction of integrated traditional Chi-nese and Western medicine treatment mode for malignant tumors,namely synergistic therapy,palliative therapy,and preventive thera-py,covering different stages of malignant tumors,in order to give full play to the advantages and characteristics of integrated traditional Chinese and Western medicine treatment in the treatment of malignant tumors.
7.Construction of a Prognostic Prediction Model of Patients with Pathologic N0 in Resected Invasive Mucinous Adenocarcinoma of the Lung
WANG ZHENG ; HE JINXIAN ; SHEN HAIBO ; CHEN XIAOHAN ; LIN CHENGBIN ; YU HONGYAN ; GAO JIAJUN ; HE XIANNENG ; SHEN WEIYU
Chinese Journal of Lung Cancer 2024;27(1):47-55
Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82%and 75.64%,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95%CI:0.741-0.889)and 0.767(95%CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.
8.Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4
Chu ZEWEN ; Zhu MIAO ; Luo YUANYUAN ; Hu YAQI ; Feng XINYI ; Shen JIACHENG ; Wang HAIBO ; Sunagawa MASATAKA ; Liu YANQING
Journal of Pharmaceutical Analysis 2024;14(8):1158-1175
Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.
9.Progress of Dual-Energy CT Virtual Noncalcium and mDixon-Quant Techniques in Multiple Myeloma
Jing SHEN ; Haibo TAO ; Kun LI ; Guanshun WANG ; Huan MA ; Yao WANG
Chinese Journal of Medical Imaging 2024;32(10):1075-1079
Multiple myeloma is a kind of hematological malignancy commonly seen in the elderly.Its main feature is that abnormal proliferation of bone marrow plasma cells replace normal bone marrow,which changes the water fat ratio of vertebral bone marrow,leading to bone destruction and bone marrow infiltration.At present,dual energy CT virtual non calcium and modified Dixon Quant can detect the changes of bone marrow and conduct qualitative and quantitative analysis of bone lesions,which can assist in the diagnosis of multiple myeloma,prompt treatment response and judge the prognosis of patients.This paper reviews the application progress of the above two quantitative techniques in multiple myeloma,in order to provide imaging reference for the diagnosis and treatment of multiple myeloma.
10.Analysis of influencing factors of community elderly health services by general practitioners from the perspective of social ecology
Haibo ZHANG ; Wenting WEN ; Jiayu CAO ; Jingjie GONG ; Shucheng XU ; Junlong SHEN ; Jun ZHAO
Chinese Journal of Hospital Administration 2023;39(2):135-140
Objective:To identify the influencing factors for community elderly health services provided by general practitioners (GPs) using the social ecological theory, for reference in improving their participation and satisfaction.Methods:According to the social ecological theory, an ecological model for GPs to carry out community elderly health services was constructed from four levels: public policy ecology, community health service ecology, interpersonal relationship ecology, and individual characteristics ecology of general practitioners. A survey questionnaire was designed with six latent variables: public health policy support, public health service and basic medical service supply, doctor-patient relationship, individual participation and individual satisfaction. The questionnaire was distributed to 220 GPs from 11 primary healthcare institutions in Jiangsu province, China, who were randomly selected between October and November 2021. Exploratory and confirmatory analyses of the model were conducted using AMOS 25.0.Results:A total of 207 valid questionnaires were collected, and all the KMO values of the six latent variables were greater than 0.7, while the composite reliability values and average variance extracted values greater than 0.7 and 0.5, respectively. Both the reliability and validity of the data met the analysis requirements. Exploratory analysis revealed that public health policy support had a direct positive effect on both public health service and basic medical service supply (both effect sizes being 0.37). Public health service had a direct positive effect on doctor-patient relationship, individual participation and individual satisfaction (effect sizes being 0.52, 0.22, and 0.31, respectively). The direct effect of basic medical service supply on doctor-patient relationship was not significant (effect size being 0.03), but it had a direct positive effect on public health service (effect size being 0.46). Doctor-patient relationship had a direct positive effect on individual participation (effect size being 0.51), but its direct effect on individual satisfaction was not significant (effect size being 0.06). Individual participation had a direct positive effect on individual satisfaction (effect size being 0.52). Conclusions:By optimizing the public policy ecosystem, community health service ecosystem, and interpersonal relationship ecosystem, the participation and satisfaction of general practitioners can be systematically improved.

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